A Preliminary Study to Evaluate the Safety, Tolerability, Preliminary Efficacy and Pharmacokinetic Profile of KQ-2002 (CD19/CD22 CAR-T) in Adults With Recurrent or Refractory Acute Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 48
- 试验地点
- 2
- 主要终点
- Incidence and severity of adverse events
研究概览
简要总结
This study examines the safety, tolerability and preliminary efficacy of anti-CD19 /CD22 CAR T cells (KQ-2002)manufactured on-site in adults with relapsed or refractory CD19+ B cell acute lymphoblastic leukemia or CD19+ B cell non Hodgkin lymphoma.
详细描述
Patients will undergo screening, leukapheresis (cell collection), lymphodepleting chemotherapy with fludarabine and cyclophosphamide, followed by the anti-CD19 KQ-2002 CAR T cell infusion. The lymphodepleting chemotherapy is administered over 3 days IV to prepare the body for the CAR T cells. The CAR-T cells are infused between 2-7 days after the last dose of chemotherapy. Patients will be followed for two years after the cell infusion on the study and for up to 15 years to monitor for potential long term side effects of cell therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female,≥18 years old;
- •Histologically confirmed diagnosis of B-ALL or B-NHL(meeting one of the following conditions):
- •Second or greater relapse (CD20 regimens must be included) OR
- •Refractory to first-line chemotherapy or relapse within 1 year OR
- •Relapse within 1 year of auto-HSCT.
- •With measurable or evaluable lesions（Dose expansion cohort） (B-ALL)
- •a. Relapse within 12 months of complete remission on first treatment OR b. Relapse after second-line treatment OR c. Relapse after auto HST OR d. Failure to achieve CR/CRi at the end of induction therapy OR e. Ph+ ALL intolerance to TKI or refractory or relapse after treatment with at least two and more TKIs.
- •ECOG 0~2
- •Estimated survival time ≥ 12 weeks;
- •Main tissues and organs function well.
排除标准
- •Subjects will be excluded related to the following prior therapy criteria:Prior treatment with bendamustine-containing or fludarabine;Anti-T-cell monoclonal antibody, donor lymphocyte infusion, and CNS radiotherapy within 8 weeks; Chemotherapy, lenalidomide, bortezomib within 2 weeks; vincristine within 1 week; glucocorticoids (prednisone ≥7.5 mg/d or equivalent) within 72 h
- •Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening), or any uncontrolled infection at screening
- •Uncontrolled, symptomatic, intercurrent illness including but not limited to angina pectoris, cerebrovascular accident or transient ischemia (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), New York Heart Association (NYHA) classification of ≥ Class III congestive heart failure, severe arrhythmia poorly controlled by medications, hepatic, renal, or metabolic disorders, and hypertension that is uncontrolled by standard therapy；
- •active bleeding, or venous thromboembolic event
- •Autoimmune diseases (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, etc.) that result in end-organ damage or require systemic application of immunosuppressive drugs
- •Central nervous system (CNS) disease or symptoms of CNS involvement
- •Pregnant or nursing (lactating) women
- •Presence of Grade 2 or above non-hematologic toxicity , alopecia and grade 2 neuropathy excluded
- •Any Iinappropriate conditions in the opinion of the PI .
结局指标
主要结局
Incidence and severity of adverse events
时间窗: Up to 15 years
Will be recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Incidence of Dose-limiting toxicity
时间窗: Up to 28 days
Will be recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
次要结局
- Persistence of CD19/CD22 CAR-T cells blood, bone marrow(up to 15 years)
- Overall response rate(up to 15 years)
- Overall survival(up to 15 years)
- Progression free survival(up to 15 years)
- MRD negative response rates（ Acute Lymphoblastic Leukemia ）(up to 15 years)
研究者
Rong Tao
Chief physician
Fudan University